At John Hopkins University, a manganese(V) imido complex [(TBP₈Cz)Mn^V(NMes)] was synthesized from the Mn(III) complex [(TBP₈Cz)MnM^III]  (Lansky, D.; Kosack, J.; Narducci Sarjeant, A.; Goldberg, D. Inorg. Chem. 2006, 45, 8477-8479). Even with a high-valent Mn^V center, the complex is very resistant to reduction. The ¹H-NMR spectrum showed a diamagnetic molecule, indicating a low-spin Mn^V (d²) species. The structure was confirmed via X-ray crystallography. The crystal contains two independent molecules, with the imido axial ligands pointing away from each other. A short Mn-N imido distance suggests a stronger pi overlap between the terminal imido ligand and the empty metal d_xz/d_yz orbitals. The metal ion is 0.55 Angstroms above the average plan of the four pyrrole N atoms.

Reactions of the Mn(V) complex with alkenes were unsuccessful. H-atom abstraction should be able to occur in this molecule, but it was completely unreactive toward even a highly reactive H-atom donor. This lack of reactivity shows that the complex cannot undergo even weak H abstraction. The explanation could be that the rate-determining step is the reduction of Mn^V to Mn^IV which is not easily reached, and therefore the thermodynamics do not favor the H abstraction. The complex is also very resistant to reduction, even as a high-valent species, as shown by the electochemical data.

Metal-DNA adducts are popular molecules for cancer treatment.  However, the metal-based drugs have been associated with unwanted side effects such as nausea, nephrotoxicity (toxicity to kidney cells), and myelosuppression (suppression of bone marrow activity).  Researchers have therefore been geared toward synthesizing metal-free cancer drugs.  A research team at the Indian Institute of Technology in Bombay  has created a new bis(phosphite) ligand) and corresponding complexes of selenium and gold with thioether functionalities (D. Suresh, Maravanji S. Balakrishna, Krishnan Rathinasamy, Dulal Panda and Joel T. Mague Dalton Trans., 2008, 2285 – 2292).

All three compounds were examined for cytotoxic activity in a HeLa (human cervix epitheloid carcinoma) cell line.  While the bis(phosphite) ligand and bis(sulfide) derivative of the ligand significantly inhibited growth of the HeLa cells, the selenium and gold complexes did not.  By testing both the bis(phosphite) ligand and bis(sulfide) derivative in the HeLa line with annexin V and a propidium iodide apoptosis detection kit, the researchers discovered that both compounds caused cell death by apoptosis, using specialized mechanisms within the cell to shed membrane-bound particles.  The creation of a cancer drug that could potentially reduce or eliminate the side effects of metal-based drugs could help make treatment more bearable for patients as well as possibly attack resistant cells more effectively.

In previous research, it was found that molecules that contain a glucose moiety can easily target the brain. Based on this, the researchers aimed to attach a glucose moiety at the 3-hydroxyl oxygen.  This glucose moiety can then be enzymatically removed once the molecule reaches the target leaving the metal binding agent. The copper complexes 3-Hydroxy-2-methyl-1-phenyl-4(1H)-pyridinone (Hppp) and 3-hydroxy-2-methyl-4(1H)-pyridinone (Hnbp) were synthesized. Copper was used as it is one of the redox active metals involved in Alzheimer’s disease and because it has a higher affinity for amerliorate toxic beta-amyloid deposits, which are found in the brains of affected patients.  It was found that the Hppp and Hnbp significantly reduced the amount of amerliorate toxic beta-amyloid deposits and there was no significant difference between the Hppp copper complex and the Hnbp copper complex in efficiency.

I found this research both interesting and important as there is currently no cure for Alzheimer’s disease. It is also interesting to see how inorganic chemistry can be applied to solving problems in medical and biological settings . I am hopeful that in a few years we will see a similar drug or concept that will help cure Alzheimer’s disease.